3-Hydroxypyridine → HCID 22046919, compound

HRID 2375179Notes

Reaction equation

HRID 2375179 reaction equation
[OH:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Cl[C:11]1[N:16]=[C:15](Cl)[CH:14]=[C:13]([Cl:18])[N:12]=1.[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>C1COCC1.C(Cl)Cl>[Cl:18][C:13]1[N:12]=[C:11]([O:1][C:2]2[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=2)[N:16]=[C:15]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[CH:14]=1

Participants

7

Reactant 4

HCID 79713-HydroxypyridineHCID 8083MorpholineHCID 24758Sodium hydrideHCID 773782,4,6-Trichloropyrimidine

Product 1

HCID 22046919HCID 22046919, compoundYield 14.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-hydroxypyridine (950 mg, 10 mmol) in anhydrous THF (50 mL) at 0° C. under the nitrogen protection was added NaH (60% in oil) (480 mg, 12 mmol). The suspension was stirred for 0.5 h at 0° C., and 2,4,6-trichloropyrimidine (1.84 g, 10 mmol) was added. After the mixture warmed to room temperature and stirred for 2 h, the reaction was quenched by ice brine and extracted with EtOAc (300 mL). The organic phase was washed with brine, dried (Na2SO4), filtered, evaporated in vacuo. The cure product was purified by flash chromatography on a column of silica gel (EtOAc-Hexane, 1:7). The product (1.80 g, 7.4 mmol) in CH2Cl2 (150 mL) at 0° C. was added slowly morpholine (2.5 g, 28 mmol). The reaction mixture was stirred at 0° C. for 1 h and another 1 h at room temperature. The mixture was washed with water. The organic phase was dried (Na2SO4), filtered and evaporated in vacuo and presented three isomers. The isomers was separated by flash chromatography on a column of silica gel (EtOAc-Hexane, 1:7 and 1:3) to obtain 4-[6-chloro-2-(pyridin-3-yloxy)-pyrimidin-4-yl]-morpholine (320 mg, 14.7%).

Workup

  1. temperatureAfter the mixture warmed to room temperature
  2. stirringstirred for 2 h
  3. customthe reaction was quenched by ice brine
  4. extractionextracted with EtOAc (300 mL)
  5. washThe organic phase was washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe cure product was purified by flash chromatography on a column of silica gel (EtOAc-Hexane, 1:7)
  10. stirringThe reaction mixture was stirred at 0° C. for 1 h and another 1 h at room temperature
  11. washThe mixture was washed with water
  12. dry with materialThe organic phase was dried (Na2SO4)
  13. filtrationfiltered
  14. customevaporated in vacuo
  15. customThe isomers was separated by flash chromatography on a column of silica gel (EtOAc-Hexane, 1:7 and 1:3)

Sources & evidence

ORD record
ord-8887cea48d6945aaa7ad6cf7eaff922f
Source dataset
uspto-grants-2008_12
Patent number
US07465725B2

Reaction notes

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